SYNOVIAL TISSUE IMPLANTS FROM PATIENTS WITH RHEUMATOID-ARTHRITIS CAUSE CARTILAGE DESTRUCTION IN KNEE JOINTS OF SCID.BG MICE

Objective. To establish in SCID.bg mice a model in which joint destruc tion is initiated by human inflammatory cells from patients with rheum atoid arthritis (RA). Methods. Development of a surgical technique and immunohistologic analysis. Results. Initial experiments with single c ell suspensions failed because more than 70% of the cells injected int raarticularly left the mouse knee joint within 16 h without causing de struction. This was observed with peripheral blood mononuclear cells, T cell lines reactive to mouse or rat collagen type ii, and synovial m ononuclear cells. Cell immigration was reduced but not prevented by pr eactivation with mitogens. In contrast, small tissue implants from hum an synovial membrane which were transferred by surgical intervention i nto mouse knee joints remained at the site of injection and could be e asily localized within the mouse joint (observation period up to 8 wee ks). The human synovial membrane implants induced pannus formation and erosion of cartilage and bone while only a mild and transient synovit is was observed with normal synovial membrane and control tissues like human thymus. The predominant cells at the site of destruction were h uman (CD68 +) and murine (Mac-2+) monocytes/macrophages. Conclusion. T he human/murine SCID arthritis is a useful model for studying pathogen etic aspects of joint destruction as well as effects of new drugs or n ovel treatment strategies.